Electromechanical and pharmacomechanical signalling pathways for conducted vasodilatation along endothelium of hamster feed arteries.

摘要: Conducted vasodilatation (CVD) reflects the initiation and rapid (>mm s(-1)) spread of hyperpolarization along endothelium into smooth muscle. The ion channels that initiate CVD remain unclear as do signalling pathways may complement electromechanical relaxation. Using isolated pressurized (75 mmHg; 37 degrees C) feed arteries (n=63; diameter: rest: 53 +/- 2 microm, maximal: 98 microm) from hamster retractor skeletal muscle, we investigated contribution calcium-activated potassium (KCa) endothelium-derived autacoids to CVD. Local delivery (1 microm micropipette tip; 500-2000 ms pulse) acetylcholine (ACh) at downstream end initiated a local increase in endothelial cell [Ca2+]i (Fura-PE3; Deltaratio 340/380 nm = 0.215 0.032) preceded entire vessel. During perifusion with KCa antagonists, iberiotoxin (5 had no effect, but charybdotoxin (CTX, 5 + apamin (APA, 10 abolished reversibly. Remarkably, this inhibition unmasked 'slow-conducted vasodilatation' (SCVD) >1200 approximately 21 s(-1) (n=27). Recorded 500 upstream ACh stimulus, rise (Deltaratio nm) 0.146 0.017; P<0.05) SCVD (Deltadiameter 14 3 by s. Before inhibition, antagonism nitric oxide synthase (Nomega-nitro-L-arginine, 250 microm; l-NNA) cyclooxygenase (indomethacin, INDO) effect on amplitude yet response duration decreased one-third (P<0.05). CTX APA perifusion, L-NNA INDO while conducted responses remained intact. Thus, triggers relaxation muscle cells vessel KCa, ensuing 'wave' Ca2+ releases promote pharmacomechanical